Chronic Obstructive Pulmonary

Disease
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Chronic obstructive pulmonary disease (COPD), also known as
chronic obstructive airway disease (COAD), is a group of
diseases characterized by the pathological limitation of airflow in
the airway that is not fully reversible. COPD is the umbrella term
for chronic bronchitis, emphysema and a range of other lung
disorders. It is most often due to tobacco smoking, but can be
due to other airborne irritants such as coal dust, asbestos or
solvents, as well as congenital conditions such as alpha-1-antitrypsin deficiency.

Signs and symptoms

The main symptoms of COPD include dyspnea (shortness of breath) lasting for
months or perhaps years, possibly accompanied by wheezing, and a persistent
cough with sputum production.It
is possible the sputum may
contain blood and become
thicker (hemoptysis), usually due
to damage of the blood vessels of
the airways. Severe COPD could
lead to cyanosis (bluish
decolorization usually in the lips
and fingers) caused by a lack of
oxygen in the blood. In extreme
cases it could lead to cor
pulmonale due to the extra work
required by the heart to get blood
to flow through the lungs.
 COPD is particularly characterised by the spirometric measurement of a ratio of
forced expiratory volume over 1 second (FEV1) to forced vital capacity (FVC)
being < 0.7 and the FEV1 < 70% of the predicted value as measured by a
plethysmograph. Other signs include a rapid breathing rate (tachypnea) and a
wheezing sound heard through a stethoscope. Pulmonary emphysema is NOT the
same as subcutaneous emphysema, which is a collection of air under the skin that
may be detected by the crepitus sounds produced on palpation.

Causes
• Cigarette smoking :
A primary risk factor of COPD is chronic tobacco
smoking. In the United States, around 90% of cases
of COPD are due to smoking .Not all smokers will
develop COPD, but continuous smokers have at
least a 25% risk.

• Occupational pollutants :
Some occupational pollutants, such as cadmium and silica, have shown to be
a contributing risk factor for COPD. The people at highest risk for these
pollutants include coal workers.

• Air pollution :
Urban air pollution may be a contributing factor for COPD as it is thought to
impair the development of the lung function. In developing countries indoor
air pollution, usually due to biomass fuel, has been linked to COPD, especially
in women.

• Genetics :
Very rarely, there may be a deficiency in an enzyme known as alpha 1-
antitrypsin which causes a form of COPD.

• Other risk factors :

Increasing age, male gender, allergy, repeated airway infection and general
impaired lung function are also related to the development of COPD.
Pathophysiology
• Chronic bronchitis :
Chronic bronchitis is defined in clinical terms as a cough with sputum
production on most days for 3 months of a year, for 2 consecutive years.

Chronic bronchitis is hallmarked by hyperplasia (increased number) and

hypertrophy (increased size) of the goblet cells (mucous gland) of the airway,
resulting in an increase in secretion of mucus which contributes to the airway
obstruction. Microscopically there is infiltration of the airway walls with
inflammatory cells, particularly neutrophils. Inflammation is followed by
scarring and remodeling that thickens the walls resulting in narrowing of the
small airway. Further progression leads to metaplasia (abnormal change in the
tissue) and fibrosis (further thickening and scarring) of the lower airway. The
consequence of these changes is a limitation of airflow.

• Emphysema :
Emphysema is defined histologically as the enlargement of the air spaces
distal to the terminal bronchioles, with destruction of their walls.

The enlarged air sacs (alveoli) of the lungs, reduces the surface area available
for the movement of gases during respiration. This ultimately leads to
dyspnea in severe cases. The exact mechanism for the development of
emphysema is not understood, although it is known to be linked with smoking
and age.

Diagnosis
The diagnosis of COPD is suggested by symptoms; it is a clinical diagnosis and no
single test is definitive. A history is taken of smoking and occupation, and a
physical examination is done. Measurement of lung function with a spirograph can
reveal the loss of lung function.

The severity of COPD can be classified as follows using post-bronchodilator

spirometry :
 Severity Post-bronchodilator FEV1 /FVC FEV1 % predicted

At risk >0.7 ≥80

Mild COPD ≤0.7 ≥80

Moderate
≤0.7 50-80
COPD
Severe COPD ≤0.7 30-50
Very Severe <30 or 30-50 with Chronic
≤0.7
COPD Respiratory Failure symptoms

• Physical examination :
A systematic review by the Rational Clinical Examination concluded that no
single medical sign or symptom can adequately exclude the diagnosis of
COPD.One study found that the presence of either "a history of smoking more
than 30 pack-years, diminished breath sounds, or peak flow less than 350
L/min" has a sensitivity of 98 percent.

Management
Although COPD is not curable, it can be controlled in a variety of ways. Clinical
practice guidelines by Global Initiative for Chronic Obstructive Lung Disease
(GOLD), a collaboration including the American National Heart, Lung, and Blood
Institute and the World Health Organization, are available.

• Smoking cessation :
Smoking cessation is one of the most important factors in slowing down the
progression of COPD. Even at a late stage of the disease it can reduce the rate
of deterioration and prolong the time taken for disability and death.

• Occupational change :
Workers may be able to transfer to a significantly less contaminated area of
the company depending on circumstances. Often however, workers may need
complete occupational change.

• Pharmacotherapy :
1. Bronchodilators :
 There are several types of bronchodilators used clinically with varying
efficacy: β2 agonists, M3 antimuscarinics, leukotriene antagonists,
cromones and xanthines.These drugs relax the smooth muscles of the
airway allowing for improved airflow. The change in FEV1 may not be
substantial, but changes in the vital capacity are significant. Many
patients feel less breathless after taking bronchodilators.

2. β2 agonists :
There are several highly specific β2 agonists available. Salbutamol
(Ventolin) is the most widely used short acting β2 agonist to provide
rapid relief and should be prescribed as a front line therapy for all
classes of patients. Other β2 agonists are Bambuterol, Clenbuterol,
Fenoterol, and Formoterol. Long acting β2 agonists (LABAs) such as
Salmeterol act too slowly to be used as relief for dypsnea so these drugs
should be used as maintenance therapy in the appropriate patient
population. The TORCH study showed that LABA therapy reduced COPD
exacerbation frequency over a 3 year period, compared to placebo .An
increased risk is associated with long acting β2 agonists due to
decreased sensitivity to inflammation so generally the use of a
concomitant corticosteroid is indicated.

3. M3 muscarinic antagonists (anticholinergics) :

Derived from the deadly agaric Amanita muscaria, specific
antimuscarinics were found to provide effective relief to COPD. Inhaled
antimuscarinics have the advantage of avoiding endocrine and exocrine
M3 receptors. The quaternary M3 muscarinic antagonist Ipratropium is
widely prescribed with the β2 agonist salbutamol. . Ipratropium is offered
combined with salbutamol (Combivent) and with fenoterol (Duovent).

Tiotropium provides improved specificity for M3 muscarinic receptors. It

is a long acting muscarinic antagonist that has shown good efficacy in
the reduction of exacerbations of COPD, especially when combined with
a LABA and inhaled steroid.

4. Cromones :
 Cromones are mast cell stabilizers that are thought to act on a chloride
channel found on mast cells that help reduce the production of histamine
and other inflammatory factors. Chromones are also thought to act on
IgE-regulated calcium channels on mast cells. Cromoglicate and
Nedocromil, which has a longer half-life, are two chromones available.

5. Leukotriene antagonists :
More recently leukotriene antagonists block the signalling molecules
used by the immune system. Montelukast, Pranlukast, Zafirlukast are
some of the leukotrienes antagonists.

6. Xanthines :
Theophylline is the prototype of the xanthine class of drug. Teas are
natural sources of methylxanthines, xanthines and caffeine while
chocolate is a source of theobromine. Caffeine is approximately 16%
metabolized into theophylline. Nebulized theophylline is used in the EMR
for treatment of dyspnea (Difficulty in breathing). Patients need
continual monitoring as theophylline has a narrow therapeutic range.
More aggressive EMR interventions include IV H1 antihistamines and IV
dexamethasone.

Theophylline works by inhibiting phosphodiesterase, and small

reductions in COPD exacerbation rates have been shown with this
medication. There are two new PD-4 inhibitors, roflumilast and cilomilast
which have been shown in separate trials to reduce COPD exacerbations,
though more studies are needed.

7. Corticosteroids :
Enteral and parenteral corticosteroid therapy has long been the mainstay
of treament of COPD, and is known to reduce hospital length of stay.
Similarly, inhaled corticosteriods (specifically glucocorticoids) act in the
inflammatory cascade and improve airway function considerably, and
have been shown in the ISOLDE trial to reduce the number of COPD
exacerbations by 25%. Corticosteroids are often combined with
bronchodilators in a single inhaler. Some of the more common inhaled
steroids in use are beclomethasone, mometasone, and fluticasone.
 Salmeterol and fluticasone are combined (Advair), however the reduction
in death from all causes among patients with COPD in the combination
therapy group did not reach the predetermined level of statistical
significance.

8. TNF antagonists :
Tumor necrosis factor antagonists (TNF) are the most recent class of
medications designed to deal with refractory cases. Tumor necrosis
factor-alpha is a cachexin or cachectin and is considered a so-called
biological drug. They are considerered immunosopressive with attendant
risks. These rather expensive drugs include infliximab, adalimumab and
etanercept.

9. Supplemental Oxygen :
In general, long-term administration of oxygen is usually reserved for
individuals with COPD who have arterial hypoxemia (PaO2 less than 55
mm Hg), or a PaO2 between 55 and 60 mm Hg with evidence of
pulmonary hypertension, cor pulmonale, or secondary erythrocytosis
(hematocrit >55%). In these patients, continuous home oxygen therapy
(for >15 h/d) sufficient to correct hypoxemia has been shown to improve
survival.

10. Vaccination :
Patients with COPD should be routinely vaccinated against influenza,
pneumococcus and other diseases to prevent illness and the possibility
of death.

11. Pulmonary rehabilitation :

Pulmonary rehabilitation is a program of disease management,
counseling and exercise coordinated to benefit the individual. Pulmonary
rehabilitation has been shown to relieve difficulties breathing and
fatigue. It has also been shown to improve the sense of control a patient
has over their disease as well as their emotions.

• Diet :
 A recent French study conducted over 12 years with almost 43,000 men
concluded that eating a Mediterranean diet "halves the risk of serious lung
disease like emphysema and bronchitis".

Prognosis
A good prognosis of COPD relies on an early diagnosis and prompt treatment.
Most patients will have improvement in lung function once treatment is started,
however eventually signs and symptoms will worsen as COPD progresses. The
median survival is about 10 years if two-thirds of expected lung function was lost
by diagnosis.

• Bronchitis :
Acute bronchitis usually resolves in 7-10 days with no underlying lung disease.
Chronic bronchitis however is dependent on early recognition and smoking
cessation which improves the outcome significantly.

• Emphysema :
The outcome is better for patients with less damage to the lung who stop
smoking immediately. Still, patients with extensive lung damage may live for
many years so predicting prognosis is difficult. Death may occur from
respiratory failure, pneumonia, or other complications.

• Asbestosis :
The outcome is clouded by the many complications associated with
asbestosis. Malignant mesothelioma is refractory to management affording
patients with 6-12 months of life expectancy upon clinical presentation.

• Pneumoconiosis :
The outcome is good for patients with minimal damage to the lung. However,
patients with extensive lung damage may live for many years so predicting
prognosis is difficult. Death may occur from respiratory failure, pneumonia,
cor pulmonale or other complications.

• Pulmonary neoplasms :
The stage of the tumor(s) has a major impact on neoplasm prognosis. Staging
is the process of determining tumor size, growth rate, potential metastasis,
lymph node involvement, treatment options and prognosis. Two-year
prognosis for limited small cell pulmonary neoplasms is twenty percent and
for extensive disease five percent. The average life expectancy for someone
with recurrent small cell pulmonary neoplasms is two to three months.

The 5-year overall survival rate for pulmonary neoplasms is 14%.

 References

http://www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_SignsAndSymptoms.html

http://www.medicinenet.com/chronic_obstructive_pulmonary_disease_copd/page4.htm

http://en.wikipedia.org/wiki/Chronic_obstructive_pulmonary_disease

http://www.medicinenet.com/chronic_obstructive_pulmonary_disease_copd/page3.htm7whatcauses

http://www.patient.co.uk/showdoc/40002357/

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
holding=npg&cmd=Retrieve&db=PubMed&list_uids=4166895&dopt=Abstract

http://www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_Treatments.html

http://www.who.int/respiratory/copd/en/

Created By:
Ahmed Hasan El-banna Sa’d
Ahmed Hamed Abd El-Fattah
Ahmed Gameel El-Beshbeeshy
Ahmed Gamal Abd El-Mon’em